Feasibility and implementation of portable confocal microscopy for point-of-care diagnosis of cutaneous lesions in a low-resource setting

In resource limited settings, portable diagnostic devices could potentially reduce the delay in obtaining histopathologic diagnosis.¹ Reflectance confocal microscopy (RCM) can noninvasively visualize dermatologic cellular details at the point of care. Previously, RCM has not been utilized in resource limited settings, in part due to high cost.² We developed a low-cost smartphone portable confocal microscope for visualizing skin at the point of care. We then investigated the feasibility of using this device at the Infectious Diseases Institute (IDI) in Uganda. We chose to study this device on HIV-infected patients with suspected Kaposi’s Sarcoma (KS), due to high prevalence of KS in East Africa and importance of histopathology for diagnosis,³ and preliminary data suggesting that confocal microscopy could be used to visualize KS-associated cellular features.⁵

In the portable confocal microscope, we used line-scanning optics with an inexpensive LED for illumination and a smartphone for detection and data management (Figure 1).⁴ In vivo imaging on intact skin was performed at depths of 25, 75, and 125 μm to evaluate features in the epidermis, dermo-epidermal junction, and dermis. Ex vivo imaging was performed with an excised biopsy placed in 1% acetic acid for 5 minutes to enhance nuclear contrast, which does not alter H&E staining. Ex vivo imaging allowed us to image deeper into the specimen, down to the layer of the subcutaneous fat.

Figure 1:

(A) Novel hand-held smartphone confocal microscope. (B) Use of the microscope in vivo in Uganda.

We evaluated a total of 363 patients with Fitzpatrick Skin Type 5 or 6. Imaging was performed by a phlebotomist (52% of samples), nurses (14%) or a physician (34%). In vivo imaging was successfully performed on 198 participants prior to biopsy (Figures 2A, B). Cellular features, including keratinocytes and dermal papillae, were appreciable only from 20 participants due to challenges in maintaining water immersion and stable contact between the skin and the objective lens. The cellular imaging was limited to the epidermis and the dermo-epidermal junction caused by light scattering in dark skin and reduced optical sectioning capability due to slit aperture.

Figure 2:

In Vivo images visualized the (A) keratinocytes (arrows pointing to dark circles) and (B) dermal-epidermal junction with dermal papillae (*). Ex Vivo images visualized the (C) epidermal cell nuclei, (D) adipocytes, (E) fibrous structure of normal dermis, and (F) irregular capillaries (dark areas irregular in size and shape).

In contrast, ex vivo imaging of the 363 patients was less limited by skin tone. In 185 patients, imaging provided sufficient resolution and contrast to visualize cellular features, including nuclei in epidermis, adipocytes, and collagen (Figures 2C, D, E), as well as irregular capillary patterns, which may be indicative of KS (Figure 2F). Ten patients had high quality images of both ex vivo and in vivo confocal microscopy.

Imaging was conducted in under 15 minutes and achieved lateral resolution of 1μm and optical sectioning of 5μm. The device cost $4,200 USD, 10–20 times less than that of a standard confocal microscope. All cadres of health workers found the device feasible to use. However, ease of use was influenced by the type of skin lesion: patches or plaques were easier to image than tumors, nodules, or oral lesions.

In conclusion, we developed a low-cost portable confocal microscope which was feasible to use in the field in Uganda. Ex vivo confocal microscopy shows promise for rapid point-of-care diagnosis. Limitations included light scattering limiting in vivo image quality in dark skin and the need for a confocal reader. Solutions include portable confocal microscopes with longer wavelength to reduce light scattering and improve imaging depth, as well as the design of artificial intelligence algorithms to interpret confocal images. Next steps include evaluation of the efficacy of portable confocal microscopy for point of care diagnosis of KS and other skin malignancies.